High mutation detection rates in cerebral cavernous malformation upon stringent inclusion criteria: one‐third of probands are minors
| العنوان: | High mutation detection rates in cerebral cavernous malformation upon stringent inclusion criteria: one‐third of probands are minors |
|---|---|
| المؤلفون: | Guntram Borck, Yorck Hellenbroich, Sigrid Tinschert, Christine Fauth, Andreas Ferbert, Erdmute Kunstmann, Sabine Hoffjan, Martina Mair, Omid Nikoubashman, Knut Brockmann, Barbara Zoll, G. Christoph Korenke, Stefanie Spiegler, Silke Pauli, Stephanie Gkalympoudis, Mark H. Ginsberg, Winnie Schröder, Jian Liu, Juliane Najm, Irene Sudholt, Peter M. Kroisel, Ute Felbor, Ulrich Sure, Susanne Munk-Schulenburg, Wolfram Henn, Irina Hüning, Sabine Rudnik-Schöneborn, Leonie Freudenberg, Michaela Wiednig, Ute Grasshoff, Miriam Elbracht |
| المساهمون: | University of Zurich, Felbor, Ute |
| المصدر: | Molecular Genetics & Genomic Medicine Molecular genetics & genomic medicine, vol 2, iss 2 Molecular genetics & genomic medicine : MGGM 2(2), 176-185 (2014). doi:10.1002/mgg3.60 |
| بيانات النشر: | Wiley, 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Proband, 2716 Genetics (clinical), Pediatrics, medicine.medical_specialty, predictive testing, 10039 Institute of Medical Genetics, Clinical Sciences, 610 Medicine & health, Medicinal and Biomolecular Chemistry, Epilepsy, 1311 Genetics, 1312 Molecular Biology, Genetics, medicine, Missense mutation, Family history, CCM1, 10. No inequality, Predictive testing, Molecular Biology, Stroke, CCM3, Genetics (clinical), CCM2, Genetic testing, HEG1, medicine.diagnostic_test, business.industry, cerebral cavernous malformation, mutation detection rate, medicine.disease, 3. Good health, Age at disease onset, Mutation (genetic algorithm), 570 Life sciences, biology, Original Article, business |
| الوصف: | Cerebral cavernous malformations (CCM) are prevalent vascular malformations occurring in familial autosomal dominantly inherited or isolated forms. Once CCM are diagnosed by magnetic resonance imaging, the indication for genetic testing requires either a positive family history of cavernous lesions or clinical symptoms such as chronic headaches, epilepsy, neurological deficits, and hemorrhagic stroke or the occurrence of multiple lesions in an isolated case. Following these inclusion criteria, the mutation detection rates in a consecutive series of 105 probands were 87% for familial and 57% for isolated cases. Thirty-one novel mutations were identified with a slight shift towards proportionally more CCM3 mutations carriers than previously published (CCM1: 60%, CCM2: 18%, CCM3: 22%). In-frame deletions and exonic missense variants requiring functional analyses to establish their pathogenicity were rare: An in-frame deletion within the C-terminal FERM domain of CCM1 resulted in decreased protein expression and impaired binding to the transmembrane protein heart of glass (HEG1). Notably, 20% of index cases carrying a CCM mutation were below age 10 and 33% below age 18 when referred for genetic testing. Since fulminant disease courses during the first years of life were observed in CCM1 and CCM3 mutation carriers, predictive testing of minor siblings became an issue. peerReviewed |
| وصف الملف: | Molec_Gen___Gen_Med___2014___Spiegler___High_mutation_detection_rates_in_cerebral_cavernous_malformation_upon_stringent.pdf - application/pdf; application/pdf |
| تدمد: | 2324-9269 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8a1a5246ea4777ff6fce26b154af875eTest https://doi.org/10.1002/mgg3.60Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....8a1a5246ea4777ff6fce26b154af875e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 23249269 |
|---|